Project 2: Continuous Low-Dose Estrogen/Progestin in Elderly Women The incidence of fractures from osteoporosis has reached epidemic proportions. The most commonly affected group is post-menopausal women and the most effective preventive measure is hormonal replacement therapy (HRT). HRT in women within 10-15 years of menopause is very effective in preventing fracture. However, few studies are available in elderly women who are more than 15 years past menopause. This is a large and growing group of persons who visit their doctors seeking prevention of fractures from osteoporosis. The clinician has few tools for prevention in these persons, and is faced with the problem of too few data to decide whether HRT in this age group will prevent bone loss. This is under study in the "StopIt" program, an NIH-funded controlled trial of conventional doses of continuous HRT (0.625 mg/d of estrogen and 5.0 mg/d of progestin) in the prevention of age-related bone loss in elderly women. The proposal described here is a 3 1/2-year, double blind, placebo controlled trial of continuous low-dose estrogen/progestin in the prevention of bone loss among elderly women. It will complement the "StopIt" studies (some of which are being conducted at this Center). The advantage of a lower dose of HRT in clinical practice should be a lower incidence of unwanted side effects, such as resumption of menses, and thus there should be better compliance with treatment. The long-term safety of the lower dose should be greater since the toxicity of HRT is dose-related.